E. col/ ENDOTOXIN SHOCK IN THE DOG; TREATMENT WITH LIDOCAINE OR INDOMETHACIN

Abstract

1 Dogs treated with lidocaine (1 mg kg-' h-1) or indomethacin (1.5 mg/kg) before and after an LD60 dose (1 mg/kg) of E. coli endotoxin survived for at least 72 h.2 Although all dogs in both treated groups survived, only those treated with indomethacin were significantly protected against the fall in the arterial blood pressure 1 to 2 min following endotoxin administration.3 Endotoxin increased the plasma prostaglandin F2Q (PGF2,) concentration in the control and lidocaine-ireated groups, however, no increase was observed with indomethacin treatment. 4 Neither lidocaine nor indomethacin alone had any significant effect on the parameters measured in this model.5 Following the administration of endotoxin, lidocaine-treated animals had significantly decreased plasma fibrinogen concentrations when compared to the other groups.6 This study suggests that lidocaine, a local anaesthetic and a drug widely used for cardiac arrhythmias, might offer protection in endotoxin shock. ImtrodUctiomPrevious work in this laboratory (Fletcher, Herman & Ramwell, 1976a;Fletcher, Ramwell & Herman, 1976b;Fletcher & Ramwell, 1977) has documented increased plasma prostaglandin concentrations following the administration of endotoxin intravenously in dogs and primates. The increases in prostglandins were related in time to changes in circulatory function. Therapeutic doses of analgesic-antipyretic drugs given before and after administration of endotoxin diminished the early haemodynamic changes and prevented the increase in the prostaglandins, but failed to improve the survival in the lethal (LD1oo) baboon model. In contrast, in the LD50 dog model, these drugs did improve the survival and the early circulatory function while inhibiting the synthesis of the prostaglandins. Although the prostaglandins were elevated as early as 1 to 2 min after the endotoxin administration, their relationship to the pathophysiology of endotoxin shock is unclear.The analgesic-antipyretic drugs do improve circulatory function and survival in canine endotoxin shock but the exact mechanism by which they exert a beneficial effect is unknown. We demonstrated (Fletcher & Ramwell, 1977) that while indomethacin or aspirin

Histological features of peritoneal lavage with ropivacaine in rats with fecal peritonitis

“…The local anesthetics increase survival in several studies on experimental models with mice 19 and dogs 20 even when administered systemically.…”

Effects of lidocaine on lipopolysaccharide-induced synovitis in horses

“…Others researchers (Takao et al, 1996), used the same dosage of lidocaine, but after exposing animals to 100% oxygen. Dogs (Fletcher and Ramwell, 1978) received a continuous infusion of lidocaine (1mg/kg/h) from 45min before to 2h after an LD 60 dose of endotoxin.…”

“…It was observed in dogs administered 1mg/kg lidocaine IV offered protection against endotoxic shock induced by LPS leading to survival, decreased plasma fibrinogen concentration (Fletcher and Ramwell, 1978) and decreased binding of endotoxin to cell membranes (Garnett et al, 1984). In the same specie, given intravenous prior to injection of monosodium urate crystals into knee joints caused inhibited leukocyte migration and phagocytosis (Paul et al, 1983).…”

A study of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) serum levels in rats subjected to fecal peritonitis and treated with intraperitoneal ropivacaine

“…10 Local anesthetics increased survival in several studies using experimental models with mice 21 and dogs 22 , even when administered systemically.…”